Metaplastic carcinomas of the breast without evidence of epithelial differentiation: a diagnostic approach for management

Rakha, Emad A.; Quinn, Cecily; Foschini, Maria Pia; Martin, Monica Muñoz; Dabbs, David J.; Lakhani, Sunil R.; Varga, Zsuzsanna; Pinder, Sarah; Schmitt, Fernando; Reis‐Filho, Jorge S.; Fox, Stephen B.; Ellis, Ian O.; Tan, Puay‐Hoon; Mihai, Raluca

doi:10.1111/his.14290

Cited by 16 publications

(21 citation statements)

References 44 publications

(106 reference statements)

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“…Their histological features and immunoprofiles are similar to those arising at other sites. Apart from the well-established subtypes of sarcoma such as angiosarcoma and malignant PT, several studies have reported a large number of undifferentiated primary breast sarcomas that are purported to arise from the mesenchymal tissue of the breast [9]. These have been variously designated as breast sarcoma, not otherwise specified (currently undifferentiated/unclassified sarcoma), fibrosarcoma, and myxofibrosarcoma [60][61][62].…”

Section: Malignant-appearing Breast Spindle Cell Lesionsmentioning

confidence: 99%

“…Molecular assays, including next-generation sequencing (NGS), may help to refine diagnosis but the significance of many of the detected genetic alterations is yet to be confirmed [72]. In practice, it is our approach that, following exclusion of all other possible diagnoses included in the list of differential diagnosis, a CK-negative malignant-appearing BSCL is most appropriately categorised and managed as spindle cell MBC using similar protocols to those used in the treatment of triple-negative IBC-NST [9].…”

Section: Categorisation Of a Malignant Scl With No Specific Morphological Ihc Or Molecular Characteristicsmentioning

confidence: 99%

“…The recognition of their epithelial nature or histogenesis relies on the demonstration of epithelial cell characteristics. This includes the presence of structures that indicate epithelial origin including ductal carcinoma in situ (DCIS), invasive breast carcinoma (IBC), no special type (NST), special type, or malignant squamous components, and/or demonstration of epithelial marker expression, including cytokeratin (CK), E-cadherin, and MUC1, on immunohistochemistry (IHC) [9,10]. Malignant BSCLs that are positive for CK IHC are categorised as invasive carcinomas (metaplastic, "mesenchymal-like", spindle cell carcinoma).…”

Section: Introductionmentioning

confidence: 99%

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Spindle cell lesions of the breast: a diagnostic approach

2021

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Spindle cell lesions of the breast comprise a heterogeneous group of lesions, ranging from reactive and benign processes to aggressive malignant tumours. Despite their rarity, they attract the attention of breast pathologists due to their overlapping morphological features and diagnostic challenges, particularly on core needle biopsy (CNB) specimens. Pathologists should recognise the wide range of differential diagnoses and be familiar with the diverse morphological appearances of these lesions to make an accurate diagnosis and to suggest proper management of the patients. Clinical history, immunohistochemistry, and molecular assays are helpful in making a correct diagnosis in morphologically challenging cases. In this review, we present our approach for the diagnosis of breast spindle cell lesions, highlighting the main features of each entity and the potential pitfalls, particularly on CNB. Breast spindle cell lesions are generally classified into two main categories: bland-appearing and malignant-appearing lesions. Each category includes a distinct list of differential diagnoses and a panel of immunohistochemical markers. In bland-appearing lesions, it is important to distinguish fibromatosis-like spindle cell metaplastic breast carcinoma from other benign entities and to distinguish fibromatosis from scar tissue. The malignant-appearing category includes spindle cell metaplastic carcinoma, stroma rich malignant phyllodes tumour, other primary and metastatic malignant spindle cell tumours of the breast, including angiosarcoma and melanoma, and benign mimics such as florid granulation tissue and nodular fasciitis.

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Section: Malignant-appearing Breast Spindle Cell Lesionsmentioning

confidence: 99%

Section: Categorisation Of a Malignant Scl With No Specific Morphological Ihc Or Molecular Characteristicsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Spindle cell lesions of the breast: a diagnostic approach

2021

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“…Despite the fact that there are still few viable treatment options for MpBC in the systemic setting, and the chemotherapy regimen as well as its efficacy are debatable, chemotherapy improves the prognosis of patients with MpBC (39). The involvement of chemotherapy in the prognosis of patients with MpBC has been described before (19). Chemotherapy was related to prolonged survival in the report of Rakha et al, albeit this impact was limited to earlystage disease (19).…”

Section: Discussionmentioning

confidence: 99%

Prognostic Factor Analysis and Model Construction of Triple-Negative Metaplastic Breast Carcinoma After Surgery

et al. 2022

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ObjectiveThe study aimed to analyze the prognostic factors of patients with triple-negative (TN) metaplastic breast carcinoma (MpBC) after surgery and to construct a nomogram for forecasting the 3-, 5-, and 8-year overall survival (OS).MethodsA total of 998 patients extracted from the Surveillance, Epidemiology, and End Results (SEER) database were assigned to either the training or validation group at random in a ratio of 7:3. The clinical characteristics of patients in the training and validation sets were compared, and multivariate Cox regression analysis was used to identify the independent risk variables for the OS of patients with TN MpBC after surgery. These selected parameters were estimated through the Kaplan–Meier (KM) curves using the log-rank test. The nomogram for predicting the OS was constructed and validated by performing the concordance index (C-index), receiver operating characteristics (ROC) curves with area under the receiver operating characteristic curves (AUC), calibration curves, and decision curve analyses (DCAs). Patients were then stratified as high-risk and low-risk, and KM curves were performed.ResultsMultivariate Cox regression analysis indicated that factors including age, marital status, clinical stage at diagnosis, chemotherapy, and regional node status were independent predictors of prognosis in patients with MpBC after surgery. Separate KM curves for the screened variables revealed the same statistical results as with Cox regression analysis. A prediction model was created and virtualized via nomogram based on these findings. For the training and validation cohorts, the C-index of the nomogram was 0.730 and 0.719, respectively. The AUC values of the 3-, 5-, and 8-year OS were 0.758, 0.757, and 0.785 in the training group, and 0.736, 0.735, and 0.736 for 3, 5, and 8 years in the validation group, respectively. The difference in the OS between the real observation and the forecast was quite constant according to the calibration curves. The generated clinical applicability of the nomogram was further demonstrated by the DCA analysis. In all the training and validation sets, the KM curves for the different risk subgroups revealed substantial differences in survival probabilities (P <0.001).ConclusionThe study showed a nomogram that was built from a parametric survival model based on the SEER database, which can be used to make an accurate prediction of the prognosis of patients with TN MpBC after surgery.

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“… 9 Those cases lacking cytokeratin expression were studied in more detail, and determined to be carcinomatous rather than true primary sarcomas in most cases, further evidencing the inter-tumor heterogeneity of breast cancer broadly, and MpBC specifically. 10 Indeed, a pure sarcoma of the breast is rare and is a diagnosis of exclusion, requiring extensive sampling; negative stains for p63 and a range of cytokeratins; and, a morphological examination for any evidence of epithelial differentiation.…”

Section: Current Histopathological Classificationmentioning

confidence: 99%

An Update on the Molecular Pathology of Metaplastic Breast Cancer

Reed

Kalaw

Lakhani

2021

BCTT

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Metaplastic breast cancer (MpBC) is a fascinating morphologic sub-type of breast cancer, characterised by intra-tumoural heterogeneity. By definition, these tumors show regions of metaplasia that can present as spindle, squamous, chondroid or even osseous differentiation. MpBC are typically triple-negative, and are therefore not targetable with hormone therapy or anti-HER2 therapies, leaving only chemotherapeutics for management. MpBC are known for their aggressive course and poor response to chemotherapy. We review herein the pathology and molecular landscape of MpBC and discuss opportunities for targetted therapies as well as immunotherapies.

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Metaplastic carcinomas of the breast without evidence of epithelial differentiation: a diagnostic approach for management

Cited by 16 publications

References 44 publications

Spindle cell lesions of the breast: a diagnostic approach

Spindle cell lesions of the breast: a diagnostic approach

Prognostic Factor Analysis and Model Construction of Triple-Negative Metaplastic Breast Carcinoma After Surgery

An Update on the Molecular Pathology of Metaplastic Breast Cancer

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